Low grade diffuse gliomas: Shared cellular composition and morphometric differences

Abstract

Low grade diffuse gliomas arising in the brain are challenging to treat because of their ability to infiltrate adjacent tissue. We attempted to clarify the cellular composition and histopathological features of low grade gliomas by utilizing morphometric and immunohistochemical analyses. Seventy-eight cases of low grade gliomas were examined including 21 diffuse astrocytomas (DA), 36 oligodendrogliomas (OL), and 21 oligoastrocytomas (OA), based on the WHO classification system. Moreover, OL were subdivided into three types based on the morphological characteristics advocated by Daumas-Duport et al.: OL type I, OL type II, and OL type III. The cellularity, nuclear form factor, and conditional entropy corresponding to the nuclear pleomorphism were measured in each sample by the image analysis software "Gunmetry." Twenty-two cases were immunohistochemically analyzed for the expression of several antigens. Morphometric data indicated that the cellularity of OL type II was significantly higher than that of DA, and that the conditional entropy of OL type III was significantly lower than that of DA. Although the results of the immunohistochemical studies were almost consistent with previous reports, there were significant differences in the expression of GFAP, nestin and p53 between DA and OL. Double immunostaining revealed that expression of Olig2 and GFAP, and Olig2 and nestin was mutually exclusive in most glioma cells. Moreover, the coexpression of nestin and GFAP occurred in DA and OA, but not in OL. We conclude that each glioma include cells expressing GFAP, cells expressing nestin, and cells expressing Olig2 in a characteristic proportion for each tumor type. We suggest that diffuse gliomas share cellular compositions in different ratios and that they can be distinguished by morphometrical analysis.

Oncogenic Signaling Is Dominant to Cell of Origin and Dictates Astrocytic or Oligodendroglial Tumor Development from Oligodendrocyte Precursor Cells

“…In line with what has been found for human astrocytic tumors compared with human oligodendroglial tumors, the mouse astrocytic tumors displayed stronger tumor cell-bound GFAP expression (Mokhtari et al, 2005). In human glioma there is an inverse correlation between nuclear OLIG2 expression and expression of both nestin and GFAP (Kinjo et al, 2008), which agrees well with our findings. OLIG2 is a transcription factor important for maturation and differentiation of the oligodendrocyte lineage (Zhou et al, 2001), and is also expressed by SVZ type C progenitor cells that develop into oligodendrocytes and early OPCs (Menn et al, 2006).…”

Utility of in situ demonstration of 1p loss and p53 overexpression in pathologic diagnosis of oligodendroglial tumors

“…The co‐localization of both antigens was exceptional, being observed only in some tumor cells of three glioblastomas. The inverse relationship has been supported by other investigators as well 35,36 . Kinjo et al .…”

“…Kinjo et al . attempted to characterize low‐grade gliomas, including diffuse astrocytoma, oligodendroglioma and oligoastrocytoma, according to the composition of GFAP‐positive, Olig2‐positive and nestin‐positive cells 36 . Astrocytic and oligodendroglial tumors share several phenotypic expressions, such as morphology and immunophenotype.…”

Diffusion kurtosis imaging of gliomas grades II and III - a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation

“…While ACs and ODs share a common histogenetic origin they differ in their histological appearances. ACs are recognized through their neoplastic astrocytes with slightly elongated nuclei on a background of multiple fibrillary dendrites expressing glial fibrillary acidic protein (GFAP) while ODs display higher cell density with monomorphic cells with uniformly round nuclei and perinuclear halos 34,40. These differences in extracellular space composition may explain differences in MD between ACs and ODs.…”